The Role of Oxidative Stress in Vision-Threatening Ophthalmic Diseases
Reactive oxygen species and oxidative stress have been directly implicated in the pathogenesis of several diseases that are the leading causes of blindness, including glaucoma, diabetic retinopathy, and AMD. In many cases, the onset of oxidative damage may precede the clinical manifestation of these conditions.
In addition to their role in the diseases discussed in the following sections, oxidative mechanisms are involved in numerous diseases of the anterior and posterior segments and are central in many inherited diseases of the eye. Future research and treatment will target these mechanisms, directly and indirectly, to aid in the management of their related conditions.
A, Localization of antioxidants in the human macula and peripheral retina. Vitamin E (blue) and selenium (red) are concentrated primarily in the retinal pigment epithelium (RPE). In the macula, carotenoids (yellow) are present in the Henle fiber layer; in the peripheral retina, they are also present in the rods. B, Localization of antioxidants in a cross section of the peripheral retina. Vitamin E and selenium remain concentrated mainly in the RPE but are also enriched in the rod outer segments. Carotenoids have been found in rod outer segments in the peripheral retina.
(Illustrations by J. Woodward, MD; courtesy of F. J. G. M. van Kuijk, MD, PhD.)
Ung L, Pattamatta U, Carnt N, Wildinson-Berka JL, Liew G, White AJR. Oxidative stress and reactive oxygen species: a review of their role in ocular disease. Clin Sci (London). 2017;131(24):2865–2883.
Reactive oxygen species’ involvement in glaucoma may pertain to their effect on the trabecular meshwork and RGCs. An increasing body of evidence suggests that trabecular dysfunction occurs following exposure of the trabecular meshwork to ROS. In addition, several reports have demonstrated the development of oxidative stress and cell loss when RGCs in culture are exposed to increased pressure.
Population-based studies on the effect of dietary antioxidants have shown conflicting results in glaucoma, and earlier studies failed to show a benefit of these antioxidants. However, a more recent study, with longer follow-up, demonstrated that the risk of developing primary open-angle glaucoma (POAG) was 20% lower in participants who consume more foods high in antioxidants. Furthermore, in patients with POAG, a similar diet reduced the risk of development of paracentral visual field defects by 44%. The mechanism of such an effect has been suggested to involve aberrant nitric oxide pathways.
Benoist d’Azy C, Pereira B, Chiambaretta F, Dutheiul F. Oxidative and anti-oxidative stress markers in chronic glaucoma: a systematic review and meta-analysis. PLoS One. 2016;11(12):e0166915.
Kang JH, Willett WC, Rosner BA, Buys E, Wiggs JL, Pasquale LR. Association of dietary nitrate intake with primary openangle glaucoma: a prospective analysis from the Nurses’ Health Study and Health Professionals Follow-up Study. JAMA Ophthalmol. 2016;134(3):294–303.
Excerpted from BCSC 2020-2021 series: Section 2 - Fundamentals and Principles of Ophthalmology. For more information and to purchase the entire series, please visit https://www.aao.org/bcsc.